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An 8-week Study to Evaluate the Dose Response of AHU377 in Combination With Valsartan 320 mg in Patients With Mild-to-moderate Systolic Hypertension

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ClinicalTrials.gov Identifier: NCT01281306
Recruitment Status : Completed
First Posted : January 21, 2011
Results First Posted : August 18, 2015
Last Update Posted : January 29, 2016
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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Brief Summary:
The purpose of the study is to evaluate dose response of blood pressure lowering for 4 doses of AHU377, given once daily (50 mg, 100 mg, 200 mg and 400 mg) in combination with a fixed dose of valsartan (320 mg).

Condition or disease Intervention/treatment Phase
Systolic Hypertension Drug: LCZ696 Drug: Valsartan Drug: AHU377 Drug: Placebo Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 910 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Multi-center, Randomized, Double-blind, Placebo and Active Controlled, Parallel Group Study to Evaluate the Dose Response of AHU377 in Combination With Valsartan 320 mg After 8 Week Treatment in Patients With Mild-to-moderate Systolic Hypertension
Study Start Date : January 2011
Actual Primary Completion Date : December 2011
Actual Study Completion Date : December 2011

Resource links provided by the National Library of Medicine

Drug Information available for: Valsartan

Arms and Interventions
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Arm Intervention/treatment
Experimental: VAL + AHU 400 mg
Participants were started with AHU377 100 mg + valsartan 160 mg every day (qd) for 1 week, then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for another week, and then were uptitrated to AHU377 400 mg + valsartan 320 mg for the remaining 6 weeks.
 Drug: Valsartan
Valsartan was supplied as tablets in blister cards in 160 mg and 320 mg strengths.

Drug: AHU377
AHU377 was supplied in tablets in blister cards in 50 mg and 100 mg strengths.
Experimental: VAL + AHU 200 mg
Participants were started with AHU377 100 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for the remaining 7 weeks.
 Drug: Valsartan
Valsartan was supplied as tablets in blister cards in 160 mg and 320 mg strengths.

Drug: AHU377
AHU377 was supplied in tablets in blister cards in 50 mg and 100 mg strengths.
Experimental: VAL + AHU 100 mg
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 100 mg + valsartan 320 mg for the remaining 7 weeks.
 Drug: Valsartan
Valsartan was supplied as tablets in blister cards in 160 mg and 320 mg strengths.

Drug: AHU377
AHU377 was supplied in tablets in blister cards in 50 mg and 100 mg strengths.
Experimental: VAL + AHU 50 mg
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 50 mg + valartan 320 mg qd for the remaining 7 weeks.
 Drug: Valsartan
Valsartan was supplied as tablets in blister cards in 160 mg and 320 mg strengths.

Drug: AHU377
AHU377 was supplied in tablets in blister cards in 50 mg and 100 mg strengths.
Experimental: VAL 320 mg
Participants were started with valsartan 160 mg qd for 1 week and then were uptitrated to valsartan 320 mg qd for the remaining 7 weeks.
 Drug: Valsartan
Valsartan was supplied as tablets in blister cards in 160 mg and 320 mg strengths.
Experimental: LCZ 400 mg
Participants were started with LCZ696 200 mg qd for 1 week and then were uptitrated to LCZ696 400 mg qd for the remaining 7 weeks.
 Drug: LCZ696
LCZ696 was supplied as tablets in blister cards in 100 mg strengths.
Experimental: Placebo
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
 Drug: Placebo
Placebo was supplied as tablets in blister cards.


Outcome Measures
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Primary Outcome Measures :
  1. Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) [ Time Frame: Baseline, 8 weeks ]
    Sitting BP measurements were performed at trough (23-26 hours post-morning dose). A negative change from baseline indicates improvement.


Secondary Outcome Measures :
  1. Change From Baseline in Mean Diastolic Blood Pressure (msDBP) [ Time Frame: Baseline, 8 weeks ]
    Sitting BP measurements were performed at trough (23-26 hours post-morning dose). A negative change from baseline indicates improvement.

  2. Change From Baseline in Mean 24 Hour Ambulatory SBP (maSBP) and Mean 24 Hour Ambulatory DBP (maDBP) [ Time Frame: Baseline, 8 weeks ]
    Twenty four hour ABPM was performed twice duirng the study at baseline and week 8. The second ABPM assessment was performed only in participants who had successfully completed the ABPM assessment at baseline. A negative change from baseline indicates improvement.

  3. Change From Baseline in Daytime maSBP and maDBP [ Time Frame: Baseline, 8 weeks ]
    Twenty four hour ABPM was performed twice during the study at baseline and week 8. The second ABPM assessment was performed only in participants who had successfully completed the ABPM assessment at baseline. A negative change from baseline indicates improvement.

  4. Change From Baseline in Nighttime maSBP and maDBP [ Time Frame: Baseline and 8 weeks ]
    Twenty four hour ABPM was performed twice duirng the study at baseline and week 8. The second ABPM assessment was performed only in participants who had successfully completed the ABPM assessment at baseline. A negative change from baseline indicates improvement.

  5. Change From Baseline in Mean Sitting Pulse Pressure [ Time Frame: Baseline, 8 weeks ]
    Pulse rate measurements were performed. A negative change from baseline indicates improvement.

  6. Change From Baseline in Mean Ambulatory Pulse Pressure [ Time Frame: Baseline, 8 weeks ]
    Pulse rate measurements were performed. A negative change from baseline indicates improvement.

  7. Change From Baseline in maSBP and maDBP in Dippers [ Time Frame: Baseline, 8 weeks ]
    Twenty four hour ABPM was performed twice during the study at baseline and week 8. The second ABPM assessment was performed only in participants who had successfully completed the ABPM assessment at baseline. Dippers were defined as participants who showed a decrease of at least 10% in maSBP during the night (10pm-6am) compared with the daytime level. A negative change from baseline indicates improvement.

  8. Change From Baseline in maSBP and maDBP in Non-dippers [ Time Frame: Baseline, 8 weeks ]
    Twenty four hour ABPM was performed twice duirng the study at baseline and week 8. The second ABPM assessment was performed only in participants who had successfully completed the ABPM assessment at baseline. Dippers were defined as participants who showed a decrease of at least 10% in maSBP during the night (10pm-6am) compared with the daytime level. A negative change from baseline indicates improvement.

  9. Change From Baseline in msSBP and msDBP in Participants < 65 Years of Age [ Time Frame: Baseline, 8 weeks ]
    Sitting BP measurements were performed at trough (23-26 hours post-morning dose). A negative change from baseline indicates improvement.

  10. Change From Baseline in msSBP and msDBP in Participants >= 65 Years of Age [ Time Frame: Baseline, 8 weeks ]
    Sitting BP measurements were performed at trough (23-26 hours post-morning dose). A negative change from baseline indicates improvement.

  11. Change From Baseline in maSBP and maDBP in Participants < 65 Years of Age [ Time Frame: Baseline, 8 weeks ]
    Twenty four hour ABPM was performed twice duirng the study at baseline and week 8. The second ABPM assessment was performed only in participants who had successfully completed the ABPM assessment at baseline. A negative change from baseline indicates improvement.

  12. Change From Baseline in maSBP and maDBP in Participants >= 65 Years of Age [ Time Frame: Baseline, 8 weeks ]
    Twenty four hour ABPM was performed twice duirng the study at baseline and week 8. The second ABPM assessment was performed only in participants who had successfully completed the ABPM assessment at baseline. A negative change from baseline indicates improvement.

  13. Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response [ Time Frame: 8 weeks ]
    Sitting BP measurements were performed at trough (23-26 hours post-morning dose). Blood pressure control was defined as msSBP/MSDBP < 140/90 mmHg. Blood pressure response in msSBP was defined as <140 mmHg or a reduction >= 20mmHg from baseline. Blood pressure response in msDBP was defined as < 90 mmHg or a reduction >= 10 mmHg from baseline.

  14. Number of Participants With Adverse Events, Serious Adverse Events and Death [ Time Frame: 8 weeks ]
    Adverse event monitoring was conducted throughout the study.


Eligibility Criteria
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Information from the National Library of Medicine

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Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent must be obtained before any assessment is performed. Patients with mild-to-moderate systolic hypertension, untreated or currently taking antihypertensive therapy.
  • Ability to communicate and comply with all study requirements and demonstrate good medication compliance (≥ 80% compliance rate) during the run-in period.

Exclusion Criteria:

  • Severe hypertension
  • History of angioedema, drug-related or otherwise, as reported by the patient.
  • Pregnant or nursing (lactating) women.
  • Women of child-bearing potential (WOCBP), UNLESS they are using adequate birth control methods.
  • History or evidence of a secondary form of hypertension.
  • Other protocol-defined inclusion/exclusion criteria may apply
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01281306


Locations
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Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
More Information
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01281306    
Other Study ID Numbers: CLCZ696A2223
2010-022326-32
First Posted: January 21, 2011    Key Record Dates
Results First Posted: August 18, 2015
Last Update Posted: January 29, 2016
Last Verified: December 2015
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
hypertension
blood pressure
LCZ696
dual-acting
neprilysin
 nep inhibitor
vasopeptidase
angiotensin receptor
angiotensin receptor neprilysin inhibitor (ARNi)
Additional relevant MeSH terms:
Layout table for MeSH terms
Hypertension
Systolic Murmurs
Vascular Diseases
Cardiovascular Diseases
Heart Murmurs
Valsartan
 Sacubitril and valsartan sodium hydrate drug combination
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action